1. Field of the Invention
This invention relates to an improved process for converting oligomers of alpha-hydroxycarboxylic acids, such as glycolic and lactic acid, to dimeric cyclic esters, such as glycolide and lactide. More particularly, the invention relates to a continuous process conducted at reduced pressures and depolymerizing temperatures in a heated columnar depolymerization zone, coupled with an essentially unheated receiver for unconverted oligomer, whereby dimeric cyclic ester is produced at high production rates and the oligomer is subjected to minimal thermal stress.
2. Description of the Related Art
Dimeric cyclic esters of hydroxycarboxylic acids such as glycolide (1,4-dioxane-2,5-dione) and lactide (1,4-dioxane-3,6-dimethyl-2,5-dione), are intermediates to high molecular weight poly (hydroxycarboxylic acids) which may be useful in biomedical and other applications because of their ability to be degraded biologically and hydrolytically to form physiologically and environmentally acceptable by-products.
The preparation of the dimeric cyclic esters of alpha-hydroxycarboxylic acids is an old and much studied process. One such scheme comprises first preparing an oligomer of the hydroxy carboxylic acid, i.e., a relatively short-chain condensation polymer thereof, then heating the polymer under reduced pressure to generate the desired cyclic ester, see for example: Gruter et al., U.S. Pat. No. 1,095,205 (1914); Lowe, U.S. Pat. No. 2,668,162 (1954); Selman, U.S. Pat. No. 3,322,791 (1967); Schmitt et al., U.S. Pat. No. 3,597,450 (1971); and Bellis, U.S. Pat. No. 4,727,163 (1988).
The above processes, spanning over 70 years of technology, involve heating the high-boiling polymeric intermediate under distillation conditions whereby the polymer thermolizes/depolymerizes to the move volatile cyclic ester, which distills from the reaction mass. Such processes suffer in that they require hours of reaction time at high temperatures for the conversion of the polymeric intermediate to the cyclic ester. Further, the rather long residence times at the high temperatures employed often result in side reactions, leading, for example, to unwanted isomers, charring of the polymer and consequently difficult to handle reactor heels.
A more recent patent, Muller, U.S. Pat. No. 5,053,522, discloses continuous and semi-continuous processes for the preparation of L-lactide: initially a quantity of L-polylactic acid (oligomer) and catalyst are added to a reactor, the reactor is heated under reduced pressure to operating temperatures and the L-lactide formed is distilled off. After a certain quantity of the product is distilled, additional L-polylactic acid is fed to the reactor. In the continuous process mode, patentee states the feed is advantageously arranged such that the volume of the reactor contents is kept constant as far as possible. Patentee also states that where the L-polylactic acid is fed batchwise, the residual volume of the reactor contents is not critical within a wide range with respect to product quality, but that it is advantageous to top off (refill) the reactor after a conversion of 50 to 90%. He further states in this regard that "It cannot be excluded that excessive lowering of the reactor contents leads to a deterioration in the product."
The disclosed process suffers in that, in all its modes of operation, at least a significant portion of the oligomer fed to the reactor is continuously under thermal stress throughout the depolymerization step, and that this eventually results in degradation products and high-boiling residues in addition to the desired lactide. That this is so becomes apparent on considering that under the so-called depolymerizing conditions, the oligomer can not only depolymerize to the lower molecule weight and more volatile cyclic ester (lactide) but that it can continue to polymerize (with loss of water, which contaminates the cyclic ester distillate) to higher molecular weight and less volatile material.
In general, high molecular weight oligomer does not yield cyclic ester as rapidly/readily as low molecular weight material. This may be attributed to the greater viscosity of the higher molecular weight material and the lesser content of terminal hydroxy groups.
It appears that for such reason those skilled in the art prefer to employ oligomers having relatively low mean molecular weights, for example, the 400 to 2000, preferably 500 to 800 polylactic acid molecular weights of Muller above. It appears, too, that the longer the oligomeric material is subjected to the thermal stress of the depolymerization temperatures the more prone it is to decompose to acidic by-products, and to lose its ability to generate cyclic ester at practical production rates and eventually to form discolored and charred reactor residues (heels).
It is also known, as disclosed in Bhatia, U.S. Pat. No. 5,023,349, to convert oligomers of alpha-carboxylic acids (glycolic, lactic) to dimeric cyclic esters (glycolide, lactide) by continuously feeding the oligomer to the top of a columnar reaction (depolymerization) zone heated at depolymerization temperatures while passing an inert gas (N.sub.2 or the like) up through the oligomeric mass to sweep the cyclic ester therefrom and form a gaseous product stream, then recovering the cyclic ester from the gaseous product stream. Any unconverted oligomer accumulates in a zone below the depolymerization zone. Although the gas-assisted process of Bhatia '349 represents a significant advance in the art in providing high conversion to and recovery of high quality dimeric cyclic ester (lactide) it has the drawback that the entraining inert gas occupies a significant portion of the reactor volume and thus limits the production rate.